FMRP regulates the subcellular distribution of cortical dendritic spine density in a non-cell-autonomous manner

Bland, Katherine M.; Aharon, Adam; Widener, Eden L.; Song, Mi-Ryoung; Casey, Zachary O.; Zuo, Yi; Vidal, George S.

doi:10.1016/j.nbd.2021.105253

Cited by 6 publications

(8 citation statements)

References 59 publications

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“…37 Thus, if the YFP-H line is any indication, we might expect the density of GFP+ neurons to increase gradually from the 1-month mark as well. Nonetheless, YFP+ neurons are still relatively sparse at 4-6 months of age, enabling detailed morphological analysis 21,37 , so we would not expect this increase to significantly hamper investigations in the GFP-M line. Nonlinear relationships : Our statistical analysis was restricted to testing linear relationships between pairs of variables, so we cannot exclude the possibility that variable pairs are related in some nonlinear way.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Approximately half of the progeny from this cross carried the transgene, as determined by genotyping of tissue acquired via ear punch (Transnetyx; probe “Thy1-3 Tg”), and as reported previously. 21 We selected two hemizygous mice at postnatal day 30 for the experiment. Selected mice were female by chance, and we did not attempt to measure the estrus cycle of the mice at this age.…”

Section: Methodsmentioning

confidence: 99%

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Simultaneous 3D Cellular Positioning and Apical Dendritic Morphology of Transgenic Fluorescent Mouse CA3 Hippocampal Pyramidal Neurons

Handwerk

Bland

Brett

et al. 2022

Preprint

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Background: Pyramidal neurons of the hippocampus are not homogeneous in their structure or function, yet the structure and function of individual neurons are well-correlated. Despite these well-known facts, few structural studies of pyramidal neuronal dendrites in the hippocampus have controlled for precise cellular position within the hippocampus along its dorsoventral (longitudinal), tangential (proximodistal), or radial axes. We believe this is largely due to technical limitations that limit positional information about the neuron, limit throughput, and limit the control of confounding variables. New method: Here, we present a simple approach to address these limitations effectively in mouse CA3, adapted from our prior work in the mouse cerebral cortex. Our approach tracks the dorsoventral, tangential, and radial positions of neurons within the hippocampus, increases the number of available neurons for analysis, and provides several new controls. Results: We demonstrate how topographic and morphological data are related to one another among mouse CA3 pyramidal neurons, in a pilot data set providing proof-of-concept. Comparison with existing methods: Other common methods of labeling neurons, such as biocytin fills or Golgi-Cox stains, are labor- or time-intensive. Here, we validate the use of the transgenic fluorescent Thy1-GFP-M line, so the labeling step is practically eliminated. Other methods section the hippocampus coronally, which distorts the dorsoventral, tangential, and radial axes. Here, we preserve all three axes. Some existing methods do not collect all sections in order, instead focusing on "more dorsal" or "more ventral" sections, for example. We preserve much more dorsoventral information. Recent work has shown that CA2 is better defined by immunohistochemical rather than neuroanatomical markers. We use that immunohistochemistry here to increase precision in defining tangential position. Other studies have not measured other, critical variables and relationships that could confound the results. Here, we assess many more of these variables and relationships to increase the rigor of our work. Conclusions: We developed a more rigorous method for preserving precise cellular positioning information among reconstructed mouse hippocampal pyramidal neurons. Although we provide several innovations in our method, each innovation identified here could independently improve the rigor and reproducibility of a wide variety of approaches for understanding the morphological heterogeneity of pyramidal neurons in the brain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Simultaneous 3D Cellular Positioning and Apical Dendritic Morphology of Transgenic Fluorescent Mouse CA3 Hippocampal Pyramidal Neurons

Handwerk

Bland

Brett

et al. 2022

Preprint

Self Cite

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“…Note that there is only one study for Brg1 and hence this is not analyzed in the review. References: Tavazoie et al ( 2005 ); Hayashi et al ( 2007 ); Meikle et al ( 2008 ); Berkel et al ( 2010 ); Luikart et al ( 2011 ); Wang et al ( 2011 ); Anderson et al ( 2012 ); Clement et al ( 2012 ); Ginsberg et al ( 2012 ); Henderson et al ( 2012 ); Schmeisser et al ( 2012 ); Bateup et al ( 2013 ); Dolan et al ( 2013 ); Haws et al ( 2014 ); Oliveira and Yasuda ( 2014 ); Pop et al ( 2014 ); Tang et al ( 2014 ); Yasuda et al ( 2014 ); Barnes et al ( 2015 ); Nie et al ( 2015 ); Spinelli et al ( 2015 ); Sugiura et al ( 2015 ); Williams et al ( 2015 ); Varea et al ( 2015 ); Hodges et al ( 2017 ); Liu et al ( 2017 ); Pyronneau et al ( 2017 ); Cox et al ( 2018 ); Jawaid et al ( 2018 ); Yan et al ( 2018 ); Arroyo et al ( 2019 ); Booker et al ( 2019 ); Gross et al ( 2019 ); Sceniak et al ( 2019 ); Skelton et al ( 2019 ); Zhang et al ( 2019 ); Banke and Barria ( 2020 ); Kulinich et al ( 2020 ); Shih et al ( 2020 ); Bland et al ( 2021 ); Schaefer et al ( 2021 ); and Sugiura et al ( 2022 ) .…”

Section: Many Upstream Regulators Of Mtorc1 Are Expressed At the Dend...mentioning

confidence: 99%

“…The average difference for all models combined across cortex and hippocampus is shown, with all studies weighted equally. References: Tavazoie et al ( 2005 ); Hayashi et al ( 2007 ); Meikle et al ( 2008 ); Verpelli et al ( 2011 ); Wang et al ( 2011 ); Wang et al ( 2014 ); Durand et al ( 2012 ); Ginsberg et al ( 2012 ); Henderson et al ( 2012 ); Bateup et al ( 2013 ); Dolan et al ( 2013 ); Pop et al ( 2014 ); Tang et al ( 2014 ); Yasuda et al ( 2014 ); Cochoy et al ( 2015 ); Nie et al ( 2015 ); Sugiura et al ( 2015 ); Sugiura et al ( 2022 ); Mei et al ( 2016 ); Hodges et al ( 2017 ); Pyronneau et al ( 2017 ); Cox et al ( 2018 ); Jawaid et al ( 2018 ); Yan et al ( 2018 ); Arroyo et al ( 2019 ); Booker et al ( 2019 ); Gross et al ( 2019 ); Banke and Barria ( 2020 ); Jacot-Descombes et al ( 2020 ); Kulinich et al ( 2020 ); Bland et al ( 2021 ); and Schaefer et al ( 2021 ).…”

Section: Many Upstream Regulators Of Mtorc1 Are Expressed At the Dend...mentioning

confidence: 99%

mTOR-Dependent Spine Dynamics in Autism

Chaudry

Vasudevan

2022

Front. Mol. Neurosci.

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Autism Spectrum Conditions (ASC) are a group of neurodevelopmental disorders characterized by deficits in social communication and interaction as well as repetitive behaviors and restricted range of interests. ASC are complex genetic disorders with moderate to high heritability, and associated with atypical patterns of neural connectivity. Many of the genes implicated in ASC are involved in dendritic spine pruning and spine development, both of which can be mediated by the mammalian target of rapamycin (mTOR) signaling pathway. Consistent with this idea, human postmortem studies have shown increased spine density in ASC compared to controls suggesting that the balance between autophagy and spinogenesis is altered in ASC. However, murine models of ASC have shown inconsistent results for spine morphology, which may underlie functional connectivity. This review seeks to establish the relevance of changes in dendritic spines in ASC using data gathered from rodent models. Using a literature survey, we identify 20 genes that are linked to dendritic spine pruning or development in rodents that are also strongly implicated in ASC in humans. Furthermore, we show that all 20 genes are linked to the mTOR pathway and propose that the mTOR pathway regulating spine dynamics is a potential mechanism underlying the ASC signaling pathway in ASC. We show here that the direction of change in spine density was mostly correlated to the upstream positive or negative regulation of the mTOR pathway and most rodent models of mutant mTOR regulators show increases in immature spines, based on morphological analyses. We further explore the idea that these mutations in these genes result in aberrant social behavior in rodent models that is due to these altered spine dynamics. This review should therefore pave the way for further research on the specific genes outlined, their effect on spine morphology or density with an emphasis on understanding the functional role of these changes in ASC.

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